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A new analysis from the COMPEL trial shows that patients with EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) who experienced non-central nervous system (CNS) progression on first-line osimertinib benefit from continuing osimertinib treatment in combination with platinum-based chemotherapy.
The study was presented at the International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer (WCLC).
The COMPEL study is a global, randomised, double-blind trial, in which adult patients with non-CNS progression on first-line osimertinib were randomised 1:1 to receive either osimertinib 80 mg once daily or placebo once daily in combination with platinum-pemetrexed chemotherapy (cisplatin 75 mg/m2 or carboplatin AUC5 + pemetrexed 500 mg/m2 every 3 weeks for 4 cycles), followed by osimertinib 80 mg once daily or placebo once daily in combination with maintenance pemetrexed (500 mg/m2 every 3 weeks) until disease progression or another discontinuation criterion was met.
The study showed that continuing osimertinib with the addition of platinum-pemetrexed chemotherapy was associated with improved progression-free survival (PFS) compared with placebo plus chemotherapy (HR: 0.43; 95% CI: 0.27–0.70); median PFS was 8.4 months with osimertinib plus chemotherapy vs. 4.4 months with placebo plus chemotherapy. Median overall survival (OS) was also longer with osimertinib plus chemotherapy (15.9 months) vs. placebo plus chemotherapy (9.8 months) (HR: 0.71; 95% CI: 0.42–1.23).
“These results indicate that resistance to first-line osimertinib may be heterogeneous, and some tumour cells remain sensitive to continued therapy,” said lead investigator Dr. Giulia Pasello of the Veneto Institute of Oncology IOV-IRCCS in Italy. “This trial supports osimertinib as a backbone treatment strategy in this setting.”
Dr. Pasello reported that the safety and tolerability profile of the combination therapy was manageable and consistent with the known safety profiles of osimertinib and chemotherapy agents. The findings also align with results from the FLAURA2 study, which showed a benefit for first-line osimertinib combined with chemotherapy.
These results may help inform treatment decisions and emphasise the importance of personalised strategies for patients with EGFRm advanced NSCLC following progression on targeted therapy, said Dr. Pasello.
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